“…MK2 regulates production of cytokines including TNF-α and IL-6 through a post-transcriptional mechanism, primarily through modulating the stability and translation of mRNA. , MK2 knockout mice were shown to be resistant to collagen-induced arthritis, a well-established disease model of rheumatoid arthritis, and also showed a much reduced production of LPS-induced TNF-α, both in vitro and in vivo. , On the basis of these observations, it has been suggested that a selective MK2 inhibitor might have equivalent clinical efficacy to a p38α inhibitor but reduce or avoid unwanted side effects that may result from interfering with other downstream effects of p38. Small molecule, ATP site binding inhibitors of MK2 have been identified, − but their cellular potency appears to be limited by unfavorable competition with ATP in the cell, and to date, none has progressed into clinical trials. , Earlier work at AstraZeneca identified an anilinoquinoline series of MK2 inhibitors that showed mainly uncompetitive behavior with respect to ATP; however the overall profile of the series meant it was unsuitable as a starting point for lead optimization . More recently a novel series of non-ATP competitive MK2 inhibitors has been reported …”